SUCCESSFUL PREVENTION OF SEVERE INFECTIONS IN JAPANESE SIBLINGS WITH IL-1 RECEPTOR-ASSOCIATED KINASE 4 DEFICIENCY

IL-1 receptor-associated kinase 4 (IRAK4) deficiency is a recently recognised immunodeficiency disorder associated with immature immunity through Toll-like receptors. We report here on Japanese siblings with IRAK4 deficiency who had favourable clinical outcomes in association with the successful prevention of Streptococcus pneumoniae infections. Case 1 A 3-year-old boy was diagnosed with IRAK4 deficiency characterised by a homozygous one base pair insertion (c 167_172insA) in exon 2 of the IRAK4 gene, and defective TNF-α and IL-6 production. His older brother had succumbed to S pneumoniae meningitis due to IRAK4 deficiency. The boy received oral administration of prophylactic antibiotics, immunoglobulin substitution (200 mg/kg per month), heptavalent-conjugated pneumococcal vaccine, and 23-valent pneumococcal vaccine to prevent bacterial infections. During treatment, anti-S pneumoniae IgG2 antibody concentration was elevated and he did not develop any severe infections. Case 2 The 22-month-old sister of case 1 was diagnosed with IRAK4 deficiency characterised by the same mutation as case 1 and she received the same preventive treatment. The concentration of her anti-S pneumoniae IgG2 antibody increased and she also did not develop any severe infections. It has been reported that children with IRAK4 deficiency develop recurrent bacterial infections, especially S pneumoniae infections, until 3 years of age and thereafter the frequency of infection is decreased. It is therefore important to prevent infections until 3 years of age. The prevention of bacterial infection in the siblings described in this report seemed to be effective. Immunoglobulin substitution and vaccination may be useful in preventing severe bacterial infections in IRAK4 patients.